rs4582709

Variant names:

• chrX-133027622-G-A
• rs4582709
• NM_031907.3:c.599C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031907.3(USP26):​c.599C>T​(p.Ser200Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: USP26 NM_031907.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 1 publications found

Genes affected

USP26 (HGNC:13485): (ubiquitin specific peptidase 26) This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases and is a deubiquitinating enzyme (DUB) with His and Cys domains. It is specifically expressed in testis tissue. Mutations in this gene have been associated with Sertoli cell-only syndrome and male infertility. [provided by RefSeq, Jul 2008]

USP26 Gene-Disease associations (from GenCC):

• spermatogenic failure, X-linked, 6

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09521747).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031907.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP26	NM_031907.3	MANE Select	c.599C>T	p.Ser200Phe	missense	Exon 6 of 6	NP_114113.1	Q9BXU7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USP26	ENST00000511190.6	TSL:2 MANE Select	c.599C>T	p.Ser200Phe	missense	Exon 6 of 6	ENSP00000423390.1	Q9BXU7
	USP26	ENST00000370832.1	TSL:6	c.599C>T	p.Ser200Phe	missense	Exon 1 of 1	ENSP00000359869.1	Q9BXU7

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.45
DANN	Benign	0.78
DEOGEN2	Benign	0.064	T
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.16
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.12
Sift	Benign	0.14	T
Sift4G	Benign	0.24	T
Polyphen		0.070	B
Vest4		0.11
MutPred		0.28		Loss of sheet (P = 0.0084)
MVP		0.58
MPC		0.072
ClinPred		0.19	T
GERP RS		-0.86
Varity_R		0.076
gMVP		0.058
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4582709; hg19: chrX-132161650;